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Responsible Business 2019

Conference

Priorities, practices and principles in a digital age

28 February 2019 - 9:30am to 5:00pm

Chatham House, London

Overview

Agenda

Speakers

Pricing and booking information

Sponsors

Media partners and supporting organizations

Venue and accommodation

Press registration

Contact us

Ever-increasing consumer, investor and employee awareness continues to drive the business case for responsible behaviour, and recent events have highlighted the growing need for corporate accountability and transparency from C-suite behaviour to global supply chain management. But what exactly are these expectations across different sectors, as the acceleration of the digital age continues to present new risks, opportunities and concerns? How can the right behaviours be encouraged? 

Furthermore, ongoing political transitions and regulatory stances over the last two years have shone a light on companies’ potential and realized impact on society. With trust in political institutions low, many are calling upon businesses not only to reflect their values but to actively bridge the governance gap on issues such as equality, sustainability and human rights, in their own business operations and beyond.  But what role should business be adopting, and what are the consequences of this trend? What are the perceived trade-offs? 

The past year has seen examples of technology leaders being held to account for the mishandling of data, global corporations taking a proactive stance on contentious political issues and executive behaviour directly impacting share price. It is critical that policy-makers and business leaders re-evaluate their priorities, practices and principles as technology and politics continue to reshape the landscape. 

The third annual Chatham House Responsible Business conference will explore key questions, including:

  • Who will lead the corporate responsibility agenda? What is driving responsible behaviour? 
  • To what extent has there been a policy retreat in this space? What has been the response to this, and what does it mean for different roles and responsibilities? 
  • What are the new priorities for responsible business in a digital age? How have recent events demonstrated a shift in expectations? 
  • How can policy-makers and companies foster the integration of human rights across global supply chains, international trade and regional business operations?
  • What is the role of corporate governance and leadership in setting standards and promoting responsible business? Is this a new era of corporate activism? 

The Chatham House Rule
To enable as open a debate as possible, this conference will be held under the Chatham House Rule.

Twitter
@CH_Events
#CHBusiness

Thursday 28 February
0920

Welcome and chair's opening remarks
Dr Robin Niblett, Director, Chatham House

Keynote address
Simon Thompson, Chairman, Rio Tinto

Questions and discussion

Session One | Leaders and Drivers
1000-1115

This opening session will examine the status of corporate leadership in responsible business, evolving policy environments and stakeholder expectations, and how they continue to shape roles and responsibilities. 

  • How are expectations for responsible business evolving? Where has this been most apparent in the past 18 months, and what is driving these shifts? 
  • Do policy and regulation continue to be effective at encouraging responsible business behaviour? Where is regulation most effective in this space? 
  • Given current political sentiments and levels of trust, what role should business play in creating a sustainable economy and a more equal society? What are the implications of this?  
  • What can business leaders learn from existing examples of corporate activism? 
  • Does a trade-off exist between responsible practices and economic competitiveness, or do commercial drivers incentivize better behaviours? How does this differ across different markets and regions?

Chair
Tamzin Booth, European Business Editor, The Economist

Speakers
Helena Morrissey, Head of Personal Investing, Legal & General Investment Management, and Founder of the 30% Club
Ioannis Ioannou, Associate Professor of Strategy and Entrepreneurship, London Business School
Phil Bloomer, Executive Director, Business & Human Rights Resource Centre​
Sue Garrard, EVP Sustainable Business and Communications, Unilever (2014-18)

Questions and discussion

1115-1145 Refreshments

Session Two | Practices and Transparency
1145-1300

This session will address regulatory frameworks and economic incentives governing responsible business conduct, as well as human rights and business operations across global supply chains. 

  • How prominent are business and human rights issues on national policy agendas? To what extent has this influenced business behaviours across different sectors and regions? 
  • What progress has been made with regards to the UN Guiding Principles for Business and Human Rights? What has most effectively driven their integration? 
  • To what extent can public opinion and public awareness help narrow the governance gap? How can investors actively promote and enforce better governance practices? 
  • Does transparency necessarily lead to accountability, and in turn increase consumer and investor trust? What are the implications of this? 
  • How can due diligence and reporting be made more efficient to enhance accountability as well as transparency across supply chains and investments? Can digital solutions be employed to achieve social and environmental best practice?

Chair
Bennett Freeman, Deputy Assistant Secretary for Democracy, Human Rights and Labor, US Department of State (1999–2001)

Speakers
Gillian Caldwell, CEO, Global Witness
Madelaine Tuininga, Head of Unit, DG Trade, European Commission
Sharan Burrow, General Secretary, International Trade Union Confederation 
Guus Houttuin, Trade Adviser, European External Action Service, and Chair, the OECD Multi-stakeholder Steering Group 

Questions and discussion

1300-1400 Lunch

Session Three | Responsibility in the Digital Age
1400-1515

This session will examine the risks and opportunities presented by digitization and other technological developments for responsible business practices. 

  • What have events over the past year indicated regarding stakeholder concerns accompanying specific technologies and business practices? How have different sectors and companies responded? 
  • What are the responsible business issues that accompany the transition to a digital-first society? What can be learned from the challenges of regulating tech titans?
  • How can businesses ensure data privacy and help customers with digital access to maintain trust and maximize benefits from digital transformation? 
  • To what extent is the proliferation of information through technology already enhancing corporate accountability and transparency? What are the risks here? 

Chair
John Thornhill, Innovation Editor, Financial Times

Speakers
Nuala O’Connor, President and CEO of the Center for Democracy and Technology
Simon McDougall, Executive Director, Technology Policy and Innovation, Information Commissioner’s Office​
Rebecca MacKinnon, Director, Ranking Digital Rights, New America
Sarah Drinkwater, Director, Tech and Society Solutions Lab, Omidyar Network

Questions and discussion

1515-1545 Afternoon refreshments

Session Four | Governance
1545-1700

This closing session will explore the role of corporate governance in setting standards and leading responsible business practices, including diversity and inclusion as well as C-suite accountability and transparency. 

  • How are businesses responding to expectations of good corporate governance and leadership in the digital age? Are businesses equipped to maintain high standards of accountability and transparency in the era of open data and social media?
  • Do business leaders have a responsibility to embody as well as promote high standards of responsible business and ethical leadership? What lessons can be learnt from corporate governance failings? 
  • What role should business leaders play in the broader political environment? Is corporate activism part of responsible governance, and what are the risks?
  • What are the best strategies to empower diversity and foster inclusion in a rapidly changing global economy? Should diversity and inclusion begin in the boardroom?

Chair
Aris Vrettos, Director of Open Programmes and International Markets, Cambridge Institute for Sustainability Leadership

Speakers
Catherine Howarth, CEO, ShareAction 
Jane Ellis, Director, GoodCorporation
Mo Ibrahim, Founder, Mo Ibrahim Foundation 
Alison Cottrell, CEO, Banking Standards Board

Questions and discussion

1700 Close of conference and drinks reception 

© The Royal Institute of International Affairs 2019

Keynote Speaker

Speakers

Phil Bloomer

Executive Director, Business & Human Rights Resource Centre

Tamzin Booth

Business Editor, The Economist

Sharan Burrow

General Secretary, International Trade Union Confederation

Gillian Caldwell

CEO, Global Witness

Alison Cottrell

CEO, Banking Standards Board

Sarah Drinkwater

Director, Tech and Society Solutions Lab, Omidyar Network

Jane Ellis

Director, GoodCorporation

Bennett Freeman

Deputy Assistant Secretary for Democracy, Human Rights and Labor, United States (1999-2001)

Sue Garrard

EVP Sustainable Business and Communications, Unilever (2014-18)

Guus Houttuin

Trade Adviser, European External Action Service, and Chair, the OECD Multi-stakeholder Steering Group

Catherine Howarth

CEO, ShareAction

Mo Ibrahim

Founder, Mo Ibrahim Foundation

Ioannis Ioannou

Associate Professor of Strategy and Entrepreneurship, London Business School

Rebecca MacKinnon

Director, Ranking Digital Rights, New America

Simon McDougall

Executive Director, Technology Policy and Innovation, Information Commissioner's Office

Dame Helena Morrissey

Head of Personal Investing, Legal & General Investment Management; Founder, 30% Club

Dr Robin Niblett CMG

Director, Chatham House

Nuala O'Connor

President and CEO, Center for Democracy & Technology

John Thornhill

Innovation Editor, Financial Times

Madelaine Tuininga

Head of Unit, DG Trade, European Commission

Aris Vrettos

Director of Open Programmes and International Markets, Cambridge Institute for Sustainability Leadership

Ways to book:

  1. Online: Click here to complete the online registration form
  2. Phone: Call Boudicca Georgii Hellberg on +44 (0) 20 7314 2785
  3. Email/Post: Download a PDF registration form, complete and return to Boudicca Georgii Hellberg via email or post: Chatham House, 10 St. James Square, London, SW1Y 4LE

Check if your organization is a member of Chatham House here.

 RATE (+VAT):
Partners and major corporate members 
All organizations£595
Standard corporate members 
Commercial organizations£1,180
Government departments/agencies/intergovernmental organizations£700
NGOs/academic institutions/associations (including not for profits and registered charities)£460
Non-members 
Commercial organizations£1,295
Government departments/agencies/intergovernmental organizations£750
NGOs/academic insitutions/associations (including not for profits and registered charities)£510
 
 

Your delegate pass includes:

  • Documentation
  • Lunch and refreshments

Travel and accommodation are not included.

If you are interested in becoming a sponsor for this event, please contact Olivia Lewis on +44 (0)20 7957 5732

If you are interested in partnering with Chatham House on this event, please contact Ayesha Arif on +44 (0)20 7957 5753

Chatham House
10 St James's Square
London
SW1Y 4LE
UK
conferences@chathamhouse.org

Telephone: +44 (0)20 7957 5643
Fax: +44 (0)20 7957 5710

If you wish to book the venue for your own event please phone +44 (0)20 7314 2764

Directions
The nearest tube station is Piccadilly Circus which is on the Piccadilly and the Bakerloo Underground lines. From Piccadilly follow Regent Street southwards towards Pall Mall and take the first road on the right called Jermyn Street. Duke of York Street is the second road on the left and leads to St James's Square. Chatham House is immediately on your right.

Map

Accommodation
Although we cannot book accommodation for delegates, we have arranged a reduced rate at some nearby hotels, where you can book your own accommodation. Please inform the hotel that you will be attending a conference at Chatham House (The Royal Institute of International Affairs) to qualify for the Institute's reduced rate.

Please note all rates are subject to availability.

Flemings Mayfair
13 Half Moon Street
Mayfair
London - W1J 7BH

Tel: + 44 (0)20 7499 2964
Fax: + 44 (0)20 7499 1817
reservations@flemings.co.uk

Classic Double without breakfast: £195 +VAT

The Cavendish London
81 Jermyn Street
London - SW1U 6JF

Tel: + 44 (0)20 7930 2111
Fax: + 44 (0)20 7839 2125
enquiry.cavendish@the-ascott.com 

Classic Room without breakfast: £195 +VAT

Book The Cavendish online

The Stafford London 
St James's Place
London - SW1A 1NJ

Tel: 020 7493 0111
Fax: 020 7493 7121
​reservations@thestaffordlondon.com

Classic Queen without breakfast: £247 +VAT
Quote Chatham House

This conference will be held under the Chatham House Rule. Information for journalists.

Press can request a press pass.

For enquiries relating to the conference agenda or sponsorship please call Olivia Lewis on +44 (0) 20 7957 5732

For registration enquiries please call Boudicca Georgii Hellberg on +44 (0) 20 7314 2785

For general enquiries please email conferences@chathamhouse.org 

Department/project




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Geneva Launch: Protecting Civilians — When is ‘Incidental Harm’ Excessive?

Research Event

14 December 2018 - 10:00am to 11:30am

Graduate Institute | Chemin Eugène-Rigot 2 | 1202 Geneva | Switzerland

Event participants

Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham House
Ezequiel Heffes, Thematic Legal Adviser, Geneva Call
Sigrid Redse Johansen, Judge Advocate General, The Norwegian Armed Forces
Chair: Elizabeth Wilmshurst, Distinguished Fellow, Chatham House
Further speakers to be announced. 

PLEASE NOTE THIS EVENT IS BEING HELD IN GENEVA.

There have been large numbers of civilian deaths in the armed conflicts in Yemen and Syria. Is international humanitarian law being ignored? 

This meeting coincides with the launch of a Chatham House research paper on the incidental harm side of the proportionality assessment which belligerents are legally required to make. The panel at the meeting will consider the types of harm that fall within the scope of proportionality assessments, what constitutes ‘excessive’ harm and measures that belligerents can take to give effect to the rule on  proportionality.

This event will be followed by a reception.

Department/project

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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London Launch: Protecting Civilians — When is ‘Incidental Harm’ Excessive?

Research Event

14 January 2019 - 5:30pm to 7:00pm

Chatham House, London

Event participants

Emanuela-Chiara Gillard, Associate Fellow, International Law Programme, Chatham House
Ezequiel Heffes, Thematic Legal Adviser, Geneva Call
Sigrid Redse Johansen, Judge Advocate General, Norwegian Armed Forces
Andrew Murdoch, Legal Director, UK Foreign & Commonwealth Office
Chair: Elizabeth Wilmshurst, Distinguished Fellow, International Law Programme, Chatham House

There have been large numbers of civilian deaths in the armed conflicts in Yemen and Syria. Is international humanitarian law being ignored?

This meeting marks the London launch of a Chatham House research paper on the incidental harm side of the proportionality assessment which belligerents are legally required to make. The panel at the meeting will consider the types of harm that fall within the scope of proportionality assessments, what constitutes ‘excessive’ harm and measures that belligerents can take to give effect to the rule on proportionality.

This event will be followed by a reception.

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




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Proportionality in the Conduct of Hostilities: The Incidental Harm Side of the Assessment

10 December 2018

Clarification of international humanitarian law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups is also crucial.

Emanuela-Chiara Gillard

Associate Fellow, International Law Programme

2018-12-10-ilp-proportionality-paper.jpg

Members of civil right defence conduct a search and rescue operation on destroyed buildings after an airstrike was carried out over the city of Jisr al-Shughur in Idlib province in Syria, on 6 May 2018. Photo: Hadi Harrat/Anadolu Agency/Getty Images.

Summary

  • Military operations are taking place with increasing frequency in densely populated areas. Such operations result in loss of life and harm to civilians, as well as damage to civilian objects, (including infrastructure providing essential services). In order to protect civilians, it is imperative that armed forces and groups comply with the rules of international humanitarian law on the conduct of hostilities, including the rule of proportionality.
  • The rule of proportionality prohibits attacks which may be expected to cause incidental loss of civilian life, injury to civilians, damage to civilian objects or a combination thereof, which would be excessive in relation to the concrete and direct military advantage anticipated. This research paper analyses the key steps that belligerents must take to give effect to the rule, with a particular focus on one side of proportionality assessments – the expected incidental harm.
  • Those undertaking proportionality assessments before or during an attack must consider whether the expected harm will be caused by the attack, and whether that harm could be expected (that is, was it reasonably foreseeable).
  • For the purpose of proportionality assessments, injury to civilians includes disease, and there is no reason in principle to exclude mental harm, even though it is currently challenging to identify and quantify it. Damage to civilian objects includes damage to elements of the natural environment.
  • Once the incidental harm to be considered has been identified, a value or weight must be assigned to it. This is then balanced against the value or weight of the military advantage anticipated from the attack to determine whether the harm would be excessive.
  • In the determination of whether the expected incidental harm would be excessive compared to the anticipated military advantage, ‘excessive’ is a wide but not indeterminate standard.
  • Belligerents should develop methodologies so that those planning and deciding attacks are provided with all necessary information on expected incidental harm, and to assist them in assigning weight to the incidental harm to be considered.
  • If it becomes apparent that the rule of proportionality will be contravened, the attack in question must be cancelled or suspended.
  • Clarification of the law is important in ensuring compliance with the rule of proportionality, but a culture of compliance within armed forces and groups, inculcated by their leaders, is also crucial.




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How Human Rights Law Is Evolving to Address Inequality

10 December 2018

Chanu Peiris

Programme Manager, International Law Programme
On the 70th anniversary of the Universal Declaration of Human Rights, Chanu Peiris examines how its principles apply to one of today’s burning political issues.

2018-12-10-UDHR.jpg

Copies of the Universal Declaration of Human Rights in a variety of languages. Photo: Getty Images.

There is growing attention to human rights in debates on economic inequality. In the UK, concerns about the disproportionate impact of economic policy on vulnerable groups have been raised recently by the UN special rapporteur on extreme poverty and human rights – who issued a statement criticizing the Conservative government’s austerity policies – as well as in a report from the UK government’s independent Equality and Human Rights Commission. These reports echo global concerns about fiscal policies, poverty and extreme economic inequality.

The Universal Declaration of Human Rights – which celebrates its 70th anniversary today – and the human rights treaties it inspired do not expressly address income and wealth gaps. But international human rights law is playing an increasing role in addressing economic polarization. Those concerned about inequality should consider how, especially over the past 25 years, the principles of socioeconomic rights have been clarified by courts and other human rights mechanisms. 

While the focus in the Global North has historically been on civil and political rights, such as the prohibition on torture or the right to fair trial, international human rights law does set out economic and social rights. For example, Article 23(4) of the Declaration – which is replicated in the International Covenant on Economic, Social and Cultural Rights and other treaties – calls for the right to collective bargaining in employment. Weakening protection in this area has been raised as a partial cause of the current escalation in income inequality. 

Human rights law also guarantees rights, including to education, healthcare and social security, that have redistributive potential and so have the potential to mitigate inequality.

Human rights law recognizes that fulfilment of economic and social rights, unlike civil and political rights, can be limited by the resources available to different states, and this conditionality – along with a lack of guidelines to assist with implementation and monitoring – has historically shielded fiscal policies from human rights scrutiny. However, attitudes have shifted.

For example, international human rights law has come to embody a commitment to tackling substantive inequalities which impair human dignity.  This requires the state regulate markets, and redistribute resources, in order to prevent discrimination against disadvantaged groups such as the poor. 

The UN Committee on Economic, Social and Cultural Rights and other human rights bodies assert that states have an immediate obligation, even during times of resource constraint, to ensure the fulfilment, without discrimination, of the minimum essential levels of socioeconomic rights, for example essential subsistence and basic shelter. Thus, austerity measures that scale back the enjoyment of rights may breach human rights standards. In order to justify such measures, governments need to first demonstrate they have considered ‘less restrictive’ avenues, including taxation options.

Although the application of human rights standards to economic policy is an emerging area, human rights campaigners have been successfully leveraging these protections to address the causes and consequences of the inequality crisis. 

For example, in case No. 66/2011 the European Committee of Social Rights overturned austerity measures that would have brought wages under the poverty level, citing breaches of labour rights and protections against discrimination. In Brazil, a coalition of civil society actors successfully used human rights standards to legitimize their critiques of a 2008 tax reform bill that would have given additional tax breaks to the wealthy while withdrawing resources for social services.

Beyond legal enforcement, framing concerns within the architecture of human rights can shift power to rights-bearers and move debates on tackling extreme inequality from the policy sphere into one where the state has a duty for which it is accountable. While the state bears primary responsibility for realizing human rights, non-state actors such as businesses have responsibilities to respect human rights. Thus, human rights can also help communities to recast the scope of the crisis to one of shared responsibility.

While human rights have seen many normative developments and advocacy successes since the adoption of the Universal Declaration of Human Rights, the last 70 years also offer several lessons and strategies to adopt going forward. 

As highlighted at a recent Chatham House event, the continued emphasis on civil and political rights in the discussion about human rights is at odds with the lived experience of individuals and communities worldwide, who may not feel their economic and material concerns are reflected in campaigns for human rights.

There will need to be a greater emphasis on adapting messaging to be more inclusive and to build alliances between disparate groups. Human rights analysis will also need to move beyond documenting the impact of systemic issues towards tackling root causes and creating a positive vision for economic inclusion and governance.




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Human Rights Impact Assessment of Trade Agreements

Research Event

26 February 2019 - 6:00pm to 7:30pm

Chatham House | 10 St James's Square | London | SW1Y 4LE

Event participants

James Harrison, Reader and Associate Professor, University of Warwick School of Law
Richard James, Evaluation Co-ordinator, Directorate-General for Trade European Commission
Jennifer Zerk, Associate Fellow, International Law Programme, Chatham House
Chair: Andrea Shemberg, Chair, Global Business Initiative on Human Rights

The idea that trade agreements should be subject to human rights impact assessment has been gathering momentum in recent years. This idea springs from concern – particularly on the part of trade unions and civil society organizations – that states are not presently doing enough to anticipate and address the human rights-related issues that arise from their trading arrangements with other countries.

This meeting will coincide with the launch of a research paper on human rights impact assessment by Dr Jennifer Zerk. It will bring together experts from law, trade policy, human rights impact assessment practice and civil society to take stock of progress so far and consider the future prospects for human rights impact assessment as a risk-analysis and policymaking tool in the trade context.  

The meeting will explore the key risks and benefits of the human rights impact assessment of trade agreements. What legal, political and practical challenges have been encountered so far? In what ways could communication, stakeholder consultation and follow-up of findings be improved? And what is needed to build political and stakeholder support for these kinds of processes?  

This meeting will be followed by a reception. 

Chanu Peiris

Programme Manager, International Law
+44 (0)20 7314 3686




ess

Power Politics Could Impede Progress on Responsible Regulation of Cyberspace

3 December 2019

Harriet Moynihan

Senior Research Fellow, International Law Programme
A new Chatham House paper examines the prospects of countries reaching agreement on issues of sovereignty and non-intervention in cyberspace in the face of persistent, low-level, state-to-state cyber attacks.

2019-11-29-Intl-Law-Cyberattacks.jpg

A computer hacked by a virus known as Petya. The Petya ransomware cyberattack hit computers of Russian and Ukrainian companies on 27 June 2017. Photo: Getty Images.

In discussions to date about how international law applies in cyberspace, commentators have tended to focus their attention on how the rules on the use of force, or the law of armed conflict, apply to cyber activities conducted by states that give rise to physical damage, injury or death.

But in practice, the vast majority of state cyberattacks fall below this threshold. Far more common are persistent, low-level attacks that may leave no physical trace but that are capable of doing significant damage to a state’s ability to control its systems, often at serious economic cost.

Such cyber incursions might include network disruptions in the operation of another government’s websites; tampering with electoral infrastructure to change or undermine the result; or using cyber means to destabilize another state’s financial sector.

For these kinds of cyber operation, the principle of sovereignty, and the principle of non-intervention in another state’s internal affairs, are the starting point.

A UN Group of Government Experts (GGE) agreed in 2013 and 2015 that the principles in the UN Charter, including sovereignty and the prohibition on intervention in another state’s affairs, apply to states’ activities in cyberspace. The 2015 GGE also recommended eleven (non-binding) norms of responsible state behaviour in cyberspace.

However, states have not yet reached agreement on how to apply these principles. Until recently, there has also been very little knowledge of what states actually do in cyberspace, as they usually conduct cyber operations covertly and have been reluctant to put their views on record.

A new Chatham House research paper analyses the application of the principles of sovereignty and non-intervention to state cyberattacks that fall below the principle of use of force. As well as analysing the application of the law in this area, the paper also makes recommendations to governments on how they might best make progress in reaching agreement in this area.

Existing rules or new rules?

As the research paper makes clear, there is currently some debate, principally between countries in the West, about the extent to which sovereignty is a legally binding rule in the context of cyberspace and, if so, how it and the principle of non-intervention might apply in practice.

In the last few years, certain states have put on record how they consider international law to apply to states’ activities in cyberspace, namely the UK, Australia, France and the Netherlands. While there may be some differences in their approaches, which are discussed in the paper, there also remains important common ground: namely, that existing international law already provides a solid framework for regulating states’ cyber activities, as it regulates every other domain of state-to-state activity.

There is also an emerging trend for states to work together when attributing cyberattacks to hostile states, enabling them to call out malign cyber activity when it violates international law. (See, for example, the joint statements made in relation to the NotPetya cyber attack and malicious cyber activity attributed to the Russian government).

However, other countries have questioned whether existing international law as it stands is capable of regulating states’ cyber interactions and have called for ‘new legal instruments’ in this area.

This includes a proposal by the Shanghai Cooperation Organization (led by Russia and China) for an International Code of Conduct on Information Security, a draft of which was submitted to the UN in 2011 and 2015, without success. The UN has also formed a new Open-Ended Working Group (OEWG) under a resolution proposed by Russia to consider how international law applies to states’ activities in cyberspace.

The resolution establishing the OEWG, which began work earlier this year, includes the possibility of the group ‘introducing changes to the rules, norms and principles of responsible behaviour of States’ agreed in the 2013 and 2015 GGE reports. In the OEWG discussions at the UN in September, several countries claimed that a new legal instrument was needed to fill the ‘legal vacuum’ (Cuba) or ‘the gap of ungoverned areas’ (Indonesia).

It would be concerning if the hard-won consensus on the application of international law to cyberspace that has been reached at past GGEs started to unravel. In contrast to 2013 and 2015, the 2017 meeting failed to reach an agreement.

On 9 December, a renewed GGE will meet in New York, but the existence of the OEWG exploring the same issues in a separate process reflects the fact that cyber norms have become an area of geopolitical rivalry.

Aside from the application of international law, states are also adopting divergent approaches to the domestic regulation of cyberspace within their own territory. The emerging trend towards a ‘splinternet’ – i.e. between states that believe the internet should be global and open on the hand, and those that favour a ‘sovereignty and control’ model on the other  – is also likely to make discussions at the GGE more challenging.

Distinct from the international law concept of sovereignty is the notion of ‘cybersovereignty’, a term coined by China to describe the wide-ranging powers it assumes under domestic law to regulate its citizens’ access to the internet and personal data within its territory. This approach is catching on (as reflected in Russia’s recently enacted ‘Sovereign Internet Law’), with other authoritarian states likely to follow suit.

The importance of non-state actors

In parallel with regional and UN discussions on how international law applies, a number of initiatives by non-state actors have also sought to establish voluntary principles about responsible state behaviour in cyberspace.

The Global Commission on the Stability of Cyberspace, a multi-stakeholder body that has proposed principles, norms and recommendations to guide responsible behaviour by all parties in cyberspace, recently published its final report. The Cybersecurity Tech Accord  aims to promote collaboration between tech companies on stability and resilience in cyberspace. President Macron’s ‘Paris Call for Trust and Security in Cyberspace’ has to date received the backing of 67 states, 139 international and civil society organizations, and 358 private-sector organizations.

It remains to be seen in the long term whether the parallel processes at the UN will work constructively together or be competitive. But notwithstanding the challenging geopolitical backdrop, the UN GGE meeting next week at the least offers states the opportunity to consolidate and build on the results of past meetings; to increase knowledge and discussion about how international law might apply; and to encourage more states to put their own views of these issues on the record.




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Deletion of fatty acid transport protein 2 (FATP2) in the mouse liver changes the metabolic landscape by increasing the expression of PPAR{alpha}-regulated genes [Lipids]

Fatty acid transport protein 2 (FATP2) is highly expressed in the liver, small intestine, and kidney, where it functions in both the transport of exogenous long-chain fatty acids and the activation of very-long-chain fatty acids. Here, using a murine model, we investigated the phenotypic impacts of deleting FATP2, followed by a transcriptomic analysis using unbiased RNA-Seq to identify concomitant changes in the liver transcriptome. WT and FATP2-null (Fatp2−/−) mice (5 weeks) were maintained on a standard chow diet for 6 weeks. The Fatp2−/− mice had reduced weight gain, lowered serum triglyceride, and increased serum cholesterol levels and attenuated dietary fatty acid absorption. Transcriptomic analysis of the liver revealed 258 differentially expressed genes in male Fatp2−/− mice and a total of 91 in female Fatp2−/− mice. These genes mapped to the following gene ontology categories: fatty acid degradation, peroxisome biogenesis, fatty acid synthesis, and retinol and arachidonic acid metabolism. Targeted RT-quantitative PCR verified the altered expression of selected genes. Of note, most of the genes with increased expression were known to be regulated by peroxisome proliferator–activated receptor α (PPARα), suggesting that FATP2 activity is linked to a PPARα-specific proximal ligand. Targeted metabolomic experiments in the Fatp2−/− liver revealed increases of total C16:0, C16:1, and C18:1 fatty acids; increases in lipoxin A4 and prostaglandin J2; and a decrease in 20-hydroxyeicosatetraenoic acid. We conclude that the expression of FATP2 in the liver broadly affects the metabolic landscape through PPARα, indicating that FATP2 provides an important role in liver lipid metabolism through its transport or activation activities.




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Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes [Cell Biology]

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.




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The testis-specific LINC component SUN3 is essential for sperm head shaping during mouse spermiogenesis [Cell Biology]

Sperm head shaping is a key event in spermiogenesis and is tightly controlled via the acrosome–manchette network. Linker of nucleoskeleton and cytoskeleton (LINC) complexes consist of Sad1 and UNC84 domain–containing (SUN) and Klarsicht/ANC-1/Syne-1 homology (KASH) domain proteins and form conserved nuclear envelope bridges implicated in transducing mechanical forces from the manchette to sculpt sperm nuclei into a hook-like shape. However, the role of LINC complexes in sperm head shaping is still poorly understood. Here we assessed the role of SUN3, a testis-specific LINC component harboring a conserved SUN domain, in spermiogenesis. We show that CRISPR/Cas9-generated Sun3 knockout male mice are infertile, displaying drastically reduced sperm counts and a globozoospermia-like phenotype, including a missing, mislocalized, or fragmented acrosome, as well as multiple defects in sperm flagella. Further examination revealed that the sperm head abnormalities are apparent at step 9 and that the sperm nuclei fail to elongate because of the absence of manchette microtubules and perinuclear rings. These observations indicate that Sun3 deletion likely impairs the ability of the LINC complex to transduce the cytoskeletal force to the nuclear envelope, required for sperm head elongation. We also found that SUN3 interacts with SUN4 in mouse testes and that the level of SUN4 proteins is drastically reduced in Sun3-null mice. Altogether, our results indicate that SUN3 is essential for sperm head shaping and male fertility, providing molecular clues regarding the underlying pathology of the globozoospermia-like phenotype.




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Dysregulation of Exosome Cargo by Mutant Tau Expressed in Human-Induced Pluripotent Stem Cell (iPSC) Neurons Revealed by Proteomics Analyses

Sonia Podvin
Apr 15, 2020; 0:RA120.002079v1-mcp.RA120.002079
Research




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The Data Must Be Accessible to All

Lila M. Gierasch
Apr 1, 2020; 19:569-570
Editorial




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DEqMS: a method for accurate variance estimation in differential protein expression analysis

Yafeng Zhu
Mar 23, 2020; 0:TIR119.001646v1-mcp.TIR119.001646
Technological Innovation and Resources




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Protecting the Cloud: Securing access to public cloud accounts

How Sophos Cloud Optix helps you secure access to your AWS, Azure and Google Cloud Platform accounts.




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Protecting the Cloud: Securing user remote access to AWS

How to create secure access to services hosted in AWS with Sophos XG Firewall.




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Learning During the Pandemic: What we wish our professors and mentors knew

Student Authors: Mayleen Cortez, Brooke Keene-Gomez, Lucy Martinez, Amaury V. Miniño, Jenna Race, Kelemua Tesfaye, and Stephanie. Blog post compiled by Melissa Gutiérrez González, Pamela E. Harris, and Alicia Prieto Langarica. In this blog we center the voices of mathematics students as … Continue reading




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Strengthening Urban Preparedness and Resilience Against Biological Threats in Accra

Invitation Only Research Event

1 March 2019 - 10:30am to 2 March 2019 - 3:00pm

Chatham House, London

Capacity to contain and respond to biological threats varies considerably across the world. Yet such preparedness is vital for prevention, impact-reduction and resilience in the face of biological events, whether they be natural or deliberate outbreaks.

Chatham House is conducting a series of meetings to strengthen urban preparedness for, and resilience against, biological threats in African countries. This meeting will examine the preparedness and prevention mechanisms in Accra, reviewing the comprehensiveness of city-level preparedness.  

This meeting will focus on the formation and implementation of city-level action plans in the context of preparedness for managing biological threats. It will also explore how local authorities are contributing to this effort with their knowledge and expertise.

Attendance at this event is by invitation only.

Nilza Amaral

Project Manager, International Security Programme




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Human Control Is Essential to the Responsible Use of Military Neurotechnology

8 August 2019

Yasmin Afina

Research Assistant, International Security Programme
The military importance of AI-connected brain–machine interfaces is growing. Steps must be taken to ensure human control at all times over these technologies.

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A model of a human brain is displayed at an exhibition in Lisbon, Portugal. Photo: Getty Images.

Technological progress in neurotechnology and its military use is proceeding apace. As early as the 1970s, brain-machine interfaces have been the subject of study. By 2014, the UK’s Ministry of Defence was arguing that the development of artificial devices, such as artificial limbs, is ‘likely to see refinement of control to provide… new ways to connect the able-bodied to machines and computers.’ Today, brain-machine interface technology is being investigated around the world, including in Russia, China and South Korea.

Recent developments in the private sector are producing exciting new capabilities for people with disabilities and medical conditions. In early July, Elon Musk and Neuralink presented their ‘high-bandwidth’ brain-machine interface system, with small and flexible electrode threads packaged into a small device containing custom chips and to be inserted and implanted into the user’s brain for medical purposes.

In the military realm, in 2018, the United States’ Defense Advanced Research Projects Agency (DARPA) put out a call for proposals to investigate the potential of nonsurgical brain-machine interfaces to allow soldiers to ‘interact regularly and intuitively with artificially intelligent, semi-autonomous and autonomous systems in a manner currently not possible with conventional interfaces’. DARPA further highlighted the need for these interfaces to be bidirectional – where information is sent both from brain to machine (neural recording) and from machine to brain (neural stimulation) – which will eventually allow machines and humans to learn from each other.

This technology may provide soldiers and commanders with a superior level of sensory sensitivity and the ability to process a greater amount of data related to their environment at a faster pace, thus enhancing situational awareness. These capabilities will support military decision-making as well as targeting processes.

Neural recording will also enable the obtention of a tremendous amount of data from operations, including visuals, real-time thought processes and emotions. These sets of data may be used for feedback and training (including for virtual wargaming and for machine learning training), as well as for investigatory purposes. Collected data will also feed into research that may help researchers understand and predict human intent from brain signals – a tremendous advantage from a military standpoint.

Legal and ethical considerations

The flip side of these advancements is the responsibilities they will impose and the risks and vulnerabilities of the technology as well as legal and ethical considerations.

The primary risk would be for users to lose control over the technology, especially in a military context; hence a fail-safe feature is critical for humans to maintain ultimate control over decision-making. Despite the potential benefits of symbiosis between humans and AI, users must have the unconditional possibility to override these technologies should they believe it is appropriate and necessary for them to do so.

This is important given the significance of human control over targeting, as well as strategic and operational decision-making. An integrated fail-safe in brain-machine interfaces may in fact allow for a greater degree of human control over critical, time-sensitive decision-making. In other words, in the event of incoming missiles alert, while the AI may suggest a specific course of action, users must be able to decide in a timely manner whether to execute it or not.

Machines can learn from coded past experiences and decisions, but humans also use gut feelings to make life and death decisions. A gut feeling is a human characteristic that is not completely transferable, as it relies on both rational and emotional traits – and is part of the ‘second-brain’ and the gut-brain axis which is currently poorly understood. It is however risky to take decisions solely on gut feelings or solely on primary brain analysis—therefore, receiving a comprehensive set of data via an AI-connected brain-machine interface may help to verify and evaluate the information in a timely manner, and complement decision-making processes. However, these connections and interactions would have to be much better understood than the current state of knowledge. 

Fail-safe features are necessary to ensure compliance with the law, including international humanitarian law and international human rights law. As a baseline, human control must be used to 1) define areas where technology may or may not be trusted and to what extent, and 2) ensure legal, political and ethical accountability, responsibility and explainability at all times. Legal and ethical considerations must be taken into account from as early as the design and conceptualizing stage of these technologies, and oversight must be ensured across the entirety of the manufacturing supply chain.  

The second point raises the need to further explore and clarify whether existing national, regional and international legal, political and ethical frameworks are sufficient to cover the development and use of these technologies. For instance, there is value in assessing to what extent AI-connected brain-machine interfaces will affect the assessment of the mental element in war crimes and their human rights implications.

In addition, these technologies need to be highly secure and invulnerable to cyber hacks. Neural recording and neural stimulation will be directly affecting brain processes in humans and if an adversary has the ability to connect to a human brain, steps need to be taken to ensure that memory and personality could not be damaged.

Future questions

Military applications of technological progress in neurotechnology is inevitable, and their implications cannot be ignored. There is an urgent need for policymakers to understand the fast-developing neurotechnical capabilities, develop international standards and best practices – and, if necessary, new and dedicated legal instruments – to frame the use of these technologies.

Considering the opportunities that brain-machine interfaces may present in the realms of security and defence, inclusive, multi-stakeholder discussions and negotiations leading to the development of standards must include the following considerations:

  • What degree of human control would be desirable, at what stage and by whom? To what extent could human users be trusted with their own judgment in decision-making processes?
  • How could algorithmic and human biases, the cyber security and vulnerabilities of these technologies and the quality of data be factored into these discussions?
  • How can ethical and legal considerations be incorporated into the design stage of these technologies?
  • How can it be ensured that humans cannot be harmed in the process, either inadvertently or deliberately?
  • Is there a need for a dedicated international forum to discuss the military applications of neurotechnology? How could these discussions be integrated to existing international processes related to emerging military applications of technological progress, such as the Convention on Certain Conventional Weapons (CCW) Group of Governmental Experts on Lethal Autonomous Weapons Systems?




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The Future of EU–US Cooperation in Space Traffic Management and Space Situational Awareness

29 August 2019

As more space activities develop, there is an increasing requirement for comprehensive space situational awareness (SSA). This paper provides an overview of the current landscape in SSA and space traffic management as well as possible scenarios for EU–US cooperation in this area. 

Alexandra Stickings

Research Fellow for Space Policy and Security, RUSI

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Deployment of the NanoRacks-Remove Debris Satellite from the International Space Station. Photo: Getty Images.

Summary

  • Space situational awareness (SSA) and space traffic management (STM) are essential for sustainable near-Earth orbit. International cooperation in SSA and STM is vital with the growing number of satellite operators and the increasingly complex space environment.
  • The various definitions of SSA and STM are ambiguous. Understanding the activities that fall under each term can better assist in finding areas for cooperation and collaboration.
  • SSA has historically been a military activity, leading to an incomplete public catalogue of its use and barriers to sharing information with other states and the commercial sector. The rise in private space actors has increased the number of commercial STM providers and, with plans in the US to move responsibility for STM to civilian control, there will likely be more opportunities for international collaboration, particularly through the EU Space Surveillance and Tracking (SST) programme.
  • Individual EU member states possess developed STM capabilities, but overall these are still some way behind those of allies such as the US. Further investment in STM infrastructure and programmes is required for the EU and individual European states to be an essential partner to the US and add value to the global effort.
  • There are worldwide challenges, both political and technical, to providing STM coverage, which may lead to a lack of collaboration and gaps in understanding of activities in orbit. Existing sensors have limitations in terms of the size of objects that can be detected and the precision with which their movements can be predicted. These capability gaps represent opportunities for the EU to contribute.
  • The EU can build on its tradition of support for openness and civil society by creating a system that fosters an environment of cooperation and collaboration involving industry, commercial STM providers and the wider international community.
  • Although collaboration in STM is vital, the EU should also aim to tackle issues within the wider definition of SSA including space weather, intelligence and the security of ground stations.
  • The EU is well placed to become a global leader in SSA and STM. However, it needs to take into consideration the current political and technical landscape when making decisions regarding investment in capabilities and the pursuit of international partnerships.




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Legal Provision for Crisis Preparedness: Foresight not Hindsight

21 April 2020

Dr Patricia Lewis

Research Director, Conflict, Science & Transformation; Director, International Security Programme
COVID-19 is proving to be a grave threat to humanity. But this is not a one-off, there will be future crises, and we can be better prepared to mitigate them.

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Examining a patient while testing for COVID-19 at the Velocity Urgent Care in Woodbridge, Virginia. Photo by Chip Somodevilla/Getty Images.

A controversial debate during COVID-19 is the state of readiness within governments and health systems for a pandemic, with lines of the debate drawn on the issues of testing provision, personal protective equipment (PPE), and the speed of decision-making.

President Macron in a speech to the nation admitted French medical workers did not have enough PPE and that mistakes had been made: ‘Were we prepared for this crisis? We have to say that no, we weren’t, but we have to admit our errors … and we will learn from this’.

In reality few governments were fully prepared. In years to come, all will ask: ‘how could we have been better prepared, what did we do wrong, and what can we learn?’. But after every crisis, governments ask these same questions.

Most countries have put in place national risk assessments and established processes and systems to monitor and stress-test crisis-preparedness. So why have some countries been seemingly better prepared?

Comparing different approaches

Some have had more time and been able to watch the spread of the disease and learn from those countries that had it first. Others have taken their own routes, and there will be much to learn from comparing these different approaches in the longer run.

Governments in Asia have been strongly influenced by the experience of the SARS epidemic in 2002-3 and - South Korea in particular - the MERS-CoV outbreak in 2015 which was the largest outside the Middle East. Several carried out preparatory work in terms of risk assessment, preparedness measures and resilience planning for a wide range of threats.

Case Study of Preparedness: South Korea

By 2007, South Korea had established the Division of Public Health Crisis Response in Korea Centers for Disease Control and Prevention (KCDC) and, in 2016, the KCDC Center for Public Health Emergency Preparedness and Response had established a round-the-clock Emergency Operations Center with rapid response teams.

KCDC is responsible for the distribution of antiviral stockpiles to 16 cities and provinces that are required by law to hold and manage antiviral stockpiles.

And, at the international level, there are frameworks for preparedness for pandemics. The International Health Regulations (IHR) - adopted at the 2005 World Health Assembly and binding on member states - require countries to report certain disease outbreaks and public health events to the World Health Organization (WHO) and ‘prevent, protect against, control and provide a public health response to the international spread of disease in ways that are commensurate with and restricted to public health risks, and which avoid unnecessary interference with international traffic and trade’.

Under IHR, governments committed to a programme of building core capacities including coordination, surveillance, response and preparedness. The UN Sendai Framework for Disaster Risk highlights disaster preparedness for effective response as one of its main purposes and has already incorporated these measures into the Sustainable Development Goals (SDGs) and other Agenda 2030 initiatives. UN Secretary-General António Guterres has said COVID-19 ‘poses a significant threat to the maintenance of international peace and security’ and that ‘a signal of unity and resolve from the Council would count for a lot at this anxious time’.

Case Study of Preparedness: United States

The National Institutes of Health (NIH) and the Center for Disease Control (CDC) established PERRC – the Preparedness for Emergency Response Research Centers - as a requirement of the 2006 Pandemic and All-Hazards Preparedness Act, which required research to ‘improve federal, state, local, and tribal public health preparedness and response systems’.

The 2006 Act has since been supplanted by the 2019 Pandemic and All-Hazards Preparedness and Advancing Innovation Act. This created the post of Assistant Secretary for Preparedness and Response (ASPR) in the Department for Health and Human Services (HHS) and authorised the development and acquisitions of medical countermeasures and a quadrennial National Health Security Strategy.

The 2019 Act also set in place a number of measures including the requirement for the US government to re-evaluate several important metrics of the Public Health Emergency Preparedness cooperative agreement and the Hospital Preparedness Program, and a requirement for a report on the states of preparedness and response in US healthcare facilities.

This pandemic looks set to continue to be a grave threat to humanity. But there will also be future pandemics – whether another type of coronavirus or a new influenza virus – and our species will be threatened again, we just don’t know when.

Other disasters too will befall us – we already see the impacts of climate change arriving on our doorsteps characterised by increased numbers and intensity of floods, hurricanes, fires, crop failure and other manifestations of a warming, increasingly turbulent atmosphere and we will continue to suffer major volcanic eruptions, earthquakes and tsunamis. All high impact, unknown probability events.

Preparedness for an unknown future is expensive and requires a great deal of effort for events that may not happen within the preparers’ lifetimes. It is hard to imagine now, but people will forget this crisis, and revert to their imagined projections of the future where crises don’t occur, and progress follows progress. But history shows us otherwise.

Preparations for future crises always fall prey to financial cuts and austerity measures in lean times unless there is a mechanism to prevent that. Cost-benefit analyses will understandably tend to prioritise the urgent over the long-term. So governments should put in place legislation – or strengthen existing legislation – now to ensure their countries are as prepared as possible for whatever crisis is coming.

Such a legal requirement would require governments to report back to parliament every year on the state of their national preparations detailing such measures as:

  • The exact levels of stocks of essential materials (including medical equipment)
  • The ability of hospitals to cope with large influx of patients
  • How many drills, exercises and simulations had been organised – and their findings
  • What was being done to implement lessons learned & improve preparedness

In addition, further actions should be taken:

  • Parliamentary committees such as the UK Joint Committee on the National Security Strategy should scrutinise the government’s readiness for the potential threats outlined in the National Risk register for Civil Emergencies in-depth on an annual basis.
  • Parliamentarians, including ministers, with responsibility for national security and resilience should participate in drills, table-top exercises and simulations to see for themselves the problems inherent with dealing with crises.
  • All governments should have a minister (or equivalent) with the sole responsibility for national crisis preparedness and resilience. The Minister would be empowered to liaise internationally and coordinate local responses such as local resilience groups.
  • There should be ring-fenced budget lines in annual budgets specifically for preparedness and resilience measures, annually reported on and assessed by parliaments as part of the due diligence process.

And at the international level:

  • The UN Security Council should establish a Crisis Preparedness Committee to bolster the ability of United Nations Member States to respond to international crisis such as pandemics, within their borders and across regions. The Committee would function in a similar fashion as the Counter Terrorism Committee that was established following the 9/11 terrorist attacks in the United States.
  • States should present reports on their level of preparedness to the UN Security Council. The Crisis Preparedness Committee could establish a group of experts who would conduct expert assessments of each member state’s risks and preparedness and facilitate technical assistance as required.
  • Regional bodies such as the OSCE, ASEAN and ARF, the AU, the OAS, the PIF etc could also request national reports on crisis preparedness for discussion and cooperation at the regional level.

COVID-19 has been referred to as the 9/11 of crisis preparedness and response. Just as that shocking terrorist attack shifted the world and created a series of measures to address terrorism, we now recognise our security frameworks need far more emphasis on being prepared and being resilient. Whatever has been done in the past, it is clear that was nowhere near enough and that has to change.

Case Study of Preparedness: The UK

The National Risk Register was first published in 2008 as part of the undertakings laid out in the National Security Strategy (the UK also published the Biological Security Strategy in July 2018). Now entitled the National Risk Register for Civil Emergencies it has been updated regularly to analyse the risks of major emergencies that could affect the UK in the next five years and provide resilience advice and guidance.

The latest edition - produced in 2017 when the UK had a Minister for Government Resilience and Efficiency - placed the risk of a pandemic influenza in the ‘highly likely and most severe’ category. It stood out from all the other identified risks, whereas an emerging disease (such as COVID-19) was identified as ‘highly likely but with moderate impact’.

However, much preparatory work for an influenza pandemic is the same as for COVID-19, particularly in prepositioning large stocks of PPE, readiness within large hospitals, and the creation of new hospitals and facilities.

One key issue is that the 2017 NHS Operating Framework for Managing the Response to Pandemic Influenza was dependent on pre-positioned ’just in case’ stockpiles of PPE. But as it became clear the PPE stocks were not adequate for the pandemic, it was reported that recommendations about the stockpile by NERVTAG (the New and Emerging Respiratory Virus Threats Advisory Group which advises the government on the threat posed by new and emerging respiratory viruses) had been subjected to an ‘economic assessment’ and decisions reversed on, for example, eye protection.

The UK chief medical officer Dame Sally Davies, when speaking at the World Health Organization about Operation Cygnus – a 2016 three-day exercise on a flu pandemic in the UK – reportedly said the UK was not ready for a severe flu attack and ‘a lot of things need improving’.

Aware of the significance of the situation, the UK Parliamentary Joint Committee on the National Security Strategy launched an inquiry in 2019 on ‘Biosecurity and human health: preparing for emerging infectious diseases and bioweapons’ which intended to coordinate a cross-government approach to biosecurity threats. But the inquiry had to postpone its oral hearings scheduled for late October 2019 and, because of the general election in December 2019, the committee was obliged to close the inquiry.




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COVID 19: Assessing Vulnerabilities and Impacts on Iraq

7 April 2020

Dr Renad Mansour

Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative

Dr Mac Skelton

Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics

Dr Abdulameer Mohsin Hussein

President of the Iraq Medical Association
Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic.

2020-04-07-Iraq-COVID-spray

Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images.

Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.

COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.

Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.

But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.

The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.

Iraq’s myriad vulnerabilities

Certain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.

Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.

The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.

Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.

This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.

But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.

As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.

The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.

Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.

However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.

COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.

The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.

This analysis was produced as part of the Iraq Initiative.




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Webinar: Assessing the Twists and Turns in the US-Iran Stalemate

Research Event

28 April 2020 - 2:00pm to 3:30pm

Event participants

Esfandyar Batmanghelidj, Founder and Publisher, Bourse & Bazaar
Nasser Hadian, Professor of Political Sciences, Faculty of Law and Political Sciences, University of Tehran
Azadeh Zamirirad, Deputy Head, Middle East and Africa Division, SWP Berlin
Ariane Tabatabai, Middle East Fellow, Alliance for Securing Democracy, US German Marshall Fund; Adjunct Senior Research Scholar, SIPA
Moderator: Sanam Vakil, Deputy Head and Senior Research Fellow, Middle East and North Africa Programme, Chatham House
The webinar will be livestreamed on the MENA Programme Facebook page.

Since the start of 2020, Iran has been beset with multiple challenges including the spread of COVID-19, economic pressure from US sanctions, parliamentary elections in February, the killing of Qassem Soleimani and an increase in tensions in Iraq. The Trump administration interprets these domestic and regional challenges faces by Iran as evidence that its maximum pressure campaign is proving to be effective.

In this webinar, speakers will examine the economic and political impact of the Trump administration's policy towards Iran. Panelists will consider how these events are impacting internal dynamics in Iran and examine the economic impact of sanctions. They will also evaluate European diplomatic efforts to preserve the Iran nuclear agreement, and consider the future trajectory of US Iran policy and the potential for escalation in the region.
 
This webinar is part of the Chatham House Middle East and North Africa Programme's Online Event Series. The event will be held on the record.

Reni Zhelyazkova

Programme Coordinator, Middle East and North Africa Programme
+44 (0)20 7314 3624




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COVID-19 Crisis – Business as Usual for Gaza?

6 May 2020

Mohammed Abdalfatah

Asfari Foundation Academy Fellow
The COVID-19 pandemic has brought unprecedented challenges, economic collapse and strict lockdowns in many parts of the world. For the people of Gaza, this reality is nothing new.

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Palestinians light fireworks above the rubble during the Muslim holy month of Ramadan amid concerns about the spread of the coronavirus disease (COVID-19), in Gaza City , 30 April 2020. Photo by Majdi Fathi/NurPhoto via Getty Images.

In August 2012, when the UN released its report Gaza in 2020: A liveable place?, they could not have imagined what the world would look like in 2020: cities under lockdown, restrictions on movement, border closures, widespread unemployment, economic collapse, fear and anxiety and, above all, uncertainty about what the future holds.

For Gaza’s population of 2 million people this reality is nothing new. The conditions that the rest of the world are currently experiencing as a result of the COVID-19 pandemic is similar to the tight blockade Gaza has been living under ever since Hamas took over in 2007. Israel has imposed severe restrictions on the movement of people and goods, youth unemployment has reached 60 per cent, and over 80 per cent of Gaza’s population are now dependent on international aid.

The people of Gaza are having to face the COVID-19 crisis already at a disadvantage, with poor infrastructure, limited resources and a shortage of the most basic services, such as water and power supply. It also has a fragile health system, with hospitals lacking essential medical supplies and equipment, as well as the capacity to deal with the outbreak as there are only 84 ICU beds and ventilators available.

 

Meanwhile, intra-Palestinian divisions have persisted and were evident in the initial reaction to the pandemic. When President Mahmoud Abbas announced a state of emergency, it took two days for the Hamas-led government in Gaza to follow suit and shut down schools and universities. They later made a separate emergency appeal to address the crisis and prepare for a COVID-19 response in Gaza. This lack of coordination is typical of the way the Palestinian Authority and Hamas approach crisis situations.

After the initial uncoordinated response, Hamas, as the de-facto ruler of Gaza, has asserted its ability to control Gaza’s borders by putting in place quarantine measures for everyone who enters the strip, whether through the Erez checkpoint with Israel or the Rafah border with Egypt. They have also assigned 21 hospitals, hotels, and schools as compulsory quarantine centres for all arrivals from abroad, who have to stay in quarantine for 21 days. In comparison, there are 20 quarantine centres in the West Bank.  These strict measures have prevented the spread of the virus in the community and confined it to the quarantine centres, with only 20 confirmed cases of COVID-19 as of 6 May. Gaza’s de-facto authorities have also been able to monitor markets and prices to ensure the availability of essential goods.

Faced with a major crisis, Al-Qassam Brigades – the armed wing of Hamas – have tried to play the role of a national army by participating in efforts to fight the pandemic. They have relatively good logistical capacity and have contributed to the construction of two quarantine facilities with a total capacity of 1,000 units to prepare for more arrivals into Gaza. At the local level, municipalities have been disinfecting public spaces and facilities in addition to disseminating information about the virus and related preventative and protective measures. Other precautionary measures put in place include closing the weekly open markets, and restricting social gatherings like weddings and funerals.

Despite COVID-19, it’s business as usual when it comes to international dealings with Gaza. The key parties in the conflict – Israel, Hamas and the Palestinian Authority – along with the main external actors – Egypt, the United Nations and Qatar – have continued to stick to their policies aimed at keeping the security situation under control and preventing further escalation. Although Israel has allowed entry of pharmaceutical supplies and medical equipment into Gaza during the pandemic, it has kept its restrictions on the movement of goods and people in place, while keeping a close eye on the development of the COVID-19 outbreak in Gaza – a major outbreak here would be a nightmare scenario for Israel.

Meanwhile, Qatar has continued to address the humanitarian and economic needs of Gaza in an attempt to ease the pressure and prevent further escalation. It has pledged $150 million over the next six months to help families in Gaza from poorer backgrounds. Gaza has also been discussed by the Middle East Quartet, as Nickolay Mladenov, the UN special coordinator for the Middle East Peace Process, expressed his concern about the risk of a disease outbreak in Gaza during a call with the members of the Quartet.

Amid the pandemic, threats are still being exchanged between Israel and Hamas. The Israeli defence minister, Naftali Bennett, requested that in return for providing humanitarian aid to Gaza, Hamas agrees to return the remains of two Israeli soldiers killed in the 2014 war. While openly rejecting Bennett's statement, the leader of Hamas in Gaza, Yahya Sinwar, has offered to move forward with a prisoner swap deal if Israel agrees to release elderly prisoners and detainees in addition to detained women and children. Though dealing with its own COVID-19 outbreak, Egypt has started to mediate between the two parties in an attempt to stabilize the situation and reach a prisoner swap deal.

In the wake of this pandemic, lessons should be learned and policies should be examined, by all parties. Firstly, Israel should re-evaluate its security measures towards Gaza by easing restrictions on movement and trade which would have a positive impact on living conditions for Gaza’s population. The current measures have proven to be unsustainable and have contributed to the endless cycle of violence. Secondly, the intra-Palestinian division should end, to save Palestinians from contradictory policies and insufficient capacity on both sides. In fact, all previous attempts have failed to end this self-destructive division and this is due to the absence of political will on both sides. Elections seem to be the only viable path towards unity. Finally, efforts by the international community should go beyond stabilizing the security situation and ongoing crisis inside Gaza, where disruption of normal life is the norm.

While the world has reacted to this pandemic with a whole host of new policies and emergency measures, it has remained business as usual when dealing with Gaza. Should COVID-19 spread in Gaza, its people – who have already paid the price of a continuous blockade and intra-Palestinian division for 13 years – will pay a heavy price yet again. However, this time it is not a crisis that they alone will have to face.




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3-year freedom from progression following 68GaPSMA PET CT triaged management in men with biochemical recurrence post radical prostatectomy. Results of a prospective multi-center trial.

Background: 68Ga PSMA PET CT (PSMA) is increasingly used in men with biochemical recurrence (BCR) post radical prostatectomy (RP), but its longer term prognostic / predictive potential in these men is unknown. The aim of this study was to evaluate the predictive value of PSMA PET for 3 year freedom from progression (FFP) in men with BCR post RP undergoing salvage radiotherapy (sRT). Methods: This prospective multi-center study enrolled 260 men between 2015 and 2017. Eligible patients were referred for PSMA with rising PSA following RP. Management following PSMA was recorded but not mandated. PSMA protocols were standardised across sites and reported prospectively. Clinical, pathological and surgical information, sRT, timing and duration of androgen deprivation (ADT), 3 year PSA results and clinical events were documented. FFP was defined as a PSA rise ≤ 0.2ng/mL above nadir post sRT, with no additional treatment. Results: The median PSA was 0.26ng/mL (IQR 0.15 - 0.59) and follow-up 38 months (IQR 31-43). PSMA was negative in 34.6% (90/260), confined to prostate fossa 21.5% (56/260), pelvic nodes 26.2% (68/260), and distant disease 17.7% (46/260). 71.5% (186/260) received sRT, 38.2% (71/186) to the fossa only, 49.4% (92/186) fossa + pelvic nodes and 12.4% (23/186) nodes alone/SBRT. PSMA was highly predictive of FFP at 3 years following sRT. Overall, FFP was achieved in 64.5% (120/186) of those who received sRT, 81% (81/100) with negative/fossa confined vs. 45% (39/86) for extra fossa disease (p<0.0001). On logistic regression PSMA was more independently predictive of FFP than established clinical predictors, including PSA, T-stage, surgical margin status or Gleason score (P < 0.002). 32% of men with a negative PSMA PET did not receive treatment. Of these, 66% (19/29) progressed, with a mean rise in PSA of 1.59ng/mL over the 3 years. Conclusion: PSMA PET result is highly predictive of FFP at 3 years in men undergoing sRT for BCR following RP. In particular, men with negative PSMA PET or disease identified as still confined to the prostate fossa demonstrate high FFP, despite receiving less extensive radiotherapy and lower rates of additional ADT than those with extra fossa disease.




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Evaluation of dosimetry, quantitative methods and test-retest variability of 18F-PI-2620 PET for the assessment of tau deposits in the human brain

18F-PI-2620 is a next generation tau positron emission tomography (PET)-tracer that has demonstrated ability to image the spatial distribution of suspected tau pathology. The objective of this study was to assess the tracer biodistribution, dosimetry and quantitative methods of 18F-PI-2620 in the human brain. Full kinetic modelling approaches to quantify tau load were investigated. Non-invasive kinetic modeling approaches and semi-quantitative methods were evaluated against the full tracer kinetics. Finally, the reproducibility of PET measurements from test and retest scans was assessed. Methods: Three healthy controls (HC) and 4 Alzheimer disease (AD) subjects underwent two dynamic PET scans including arterial sampling. Distribution volume ratio (DVR) was estimated using full tracer kinetics (2 Tissue Compartment (2TC) models, Logan Graphical Analysis (LGA)) and non-invasive kinetic models (Non-Invasive Logan Graphical Analysis (NI-LGA) and the multilinear reference tissue model (MRTM2)). Standardized uptake value ratio (SUVR) was determined at different imaging windows after injection. Correlation between DVR and SUVR, effect size (Cohen’s d) and test-retest variability (TRV) were evaluated. Additionally, 6 HC subjects received one tracer administration and underwent whole-body PET for dosimetry calculation. Organ doses and the whole-body effective dose were calculated using OLINDA 2.0. Results: Strong correlation was found across different kinetic models (R2 >0.97) and between DVR(2TC) and SUVRs between 30 to 90 min with R2>0.95. Secular equilibrium was reached around 40 min post injection (p.i.) in most regions and subjects. The TRV and effect size for the SUVR across different regions was similar at 30-60 min (TRV=3.8%, d=3.80), 45-75 min (TRV=4.3%, d=3.77) and 60-90 min (TRV=4.9%, d=3.73) and increased at later time points. Elimination was via the hepatobiliary and urinary system. The whole-body effective dose was determined to be 33.3±2.1 μSv/MBq for an adult female and 33.1±1.4 μSv/MBq for an adult male with a 1.5 hour urinary bladder voiding interval. Conclusion: 18F-PI-2620 exhibits fast kinetics, suitable dosimetry and low TRV. DVR measured using the 2TC model with arterial sampling correlated strongly with DVR measured by NI-LGA, MRTM2 and SUVR. SUVR can be used for 18F-PI-2620 PET quantification of tau deposits avoiding arterial blood sampling. Static 18F-PI-2620 PET scans between 45-75min p.i. provide excellent quantification accuracy, large effect size and low TRV.




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Initial studies with [11C]vorozole positron emission tomography detect over-expression of intra-tumoral aromatase in breast cancer

Introduction: Aromatase inhibitors are the mainstay of hormonal therapy in estrogen receptor positive, postmenopausal breast cancer, although response rate is just over 50%. The goal of the present study was to validate and optimize positron emission tomography (PET) with 11C-vorozole for measuring aromatase expression in postmenopausal breast cancer. Methods: Ten newly diagnosed, postmenopausal women with biopsy confirmed breast cancer were administered 11C-vorozole intravenously and PET emission data collected between 40 – 90 minutes post-injection. Tracer injection and scanning were repeated 2 hours after ingestion of 2.5mg letrozole p.o. Mean and maximal standard uptake values and ratios to non-tumor tissue (SUVs, SUVRs) were calculated for tumor and non-tumor regions at baseline and after letrozole. Biopsy specimens from the same tumors were stained for aromatase using immunohistochemistry and evaluated for stain intensity and the percentage of immune-positive cells. Results: Seven of the 10 women (70%) demonstrated increased focal uptake of tracer (SUVR>1.1) coinciding with the mammographic location of the lesion. The other 3 women (30%) did not show increased uptake in the tumor (SUVR <1.0). All of the cases with SUVR above 1.1 had SUVs above 2.4 and there was no overlap in SUV between the two groups, with mean SUV in tumors overexpressing aromatase (SUVR>1.1) ranging from 2.47 to 13.6, while tumors not overexpressing aromatase (SUVR<1) ranged from 0.8 to 1.8. Pretreatment with letrozole reduced tracer uptake in the majority of subjects; although the %blocking varied across and within tumors. Tumors with high SUV in vivo also showed high staining intensity on IHC. Conclusion: PET with 11C-vorozole is a useful technique for measuring aromatase expression in individual breast lesions, enabling a non-invasive quantitative measurement of baseline and post-treatment aromatase availability in primary tumors and metastatic lesions.




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Diagnostic value of 68Ga-PSMA PET/CT for detection of PTEN expression in prostate cancer: a pilot study

Purpose: To explore the value of 68Ga-PSMA-PET/CT for detection of phosphatase and tensin homolog (PTEN) - loss prostate cancer (PCa). Methods: We retrospectively enrolled 75 patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET/CT before radical prostatectomy. Lesions were outlined on pathological images and regions of interest were drawn on matched mpMRI and PET/CT images. Imaging parameters including average apparent diffusion coefficient (ADCmean) and maximum standardized uptake value (SUVmax) were derived. Immunohistochemical staining was carried out to evaluate the PTEN status. The diagnostic performance of imaging parameters was analyzed by receiver operating characteristics (ROC) analysis. A univariate logistic regression analyses were used to evaluate the association between clinical and imaging variables and PTEN status. Results: Totally, 103 lesions from 54 patients were analyzed. Of these lesions, 34 of 103 (33.0%) showed PTEN-loss status. Our study showed a strong association between SUVmax and PTEN-loss tumors both in the per-patient analysis (P < 0.01) and per-lesion analysis (P < 0.01), yielding the sensitivity and specificity of 0.80 and 0.77 in the per-patient analysis and 0.83 and 0.74 in the per-lesion analysis. Meanwhile, higher pathological PSMA expression was found in the PTEN-deficiency tumors. However, there was no significant difference between PTEN-loss tumors and PTEN-intact tumors using parameters including ADCmean (P > 0.05) and PI-RADS score (P > 0.05). Surprisingly, SUVmax was a significant predictor for detection of PTEN-loss tumors (odds ratio: 7.56, 95% confidence interval: 2.18-26.24, per-patient analysis; odds ratio: 13.66, 95% confidence interval: 4.32-43.24, per-lesion analysis). Conclusion: 68Ga-PSMA-PET/CT could effectively detect aggressive PTEN-loss tumors.




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Differential expression of glucose transporters and hexokinases in prostate cancer with a neuroendocrine gene signature: a mechanistic perspective for FDG imaging of PSMA-suppressed tumors

Purpose: Although the incidence of de novo neuroendocrine prostate cancer (NEPC) is rare, recent data suggests that low expression of prostate-specific membrane antigen (PSMA) is associated with a spectrum of neuroendocrine (NE) hallmarks and androgen receptor (AR)-suppression in prostate cancer (PC). Previous clinical reports indicate that PCs with a phenotype similar to NE tumors can be more amenable to imaging by 18F-Fluorodeoxyglucose (FDG) rather than PSMA-targeting radioligands. In this study, we evaluated the association between NE gene signature and FDG uptake-associated genes including glucose transporters (GLUTs) and hexokinases, with the goal of providing a genomic signature to explain the reported FDG-avidity of PSMA-suppressed tumors. Methods: Data mining approaches, cell lines and patient-derived xenograft (PDX) models were used to study the levels of 14 members of the SLC2A family (encoding GLUT proteins), 4 members of the hexokinase family (genes: HK1 to 3 and GCK) and PSMA (FOLH1 gene) following AR-inhibition and in correlation with NE hallmarks. Also, we characterize a NE-like PC (NELPC) subset among a cohort of primary and metastatic PC samples with no NE histopathology. We measured glucose uptake in a NE-induced in vitro model and a zebrafish model by non-radioactive imaging of glucose uptake using fluorescent glucose bioprobe, GB2-Cy3. Results: This work demonstrates that a NE gene signature associates with differential expression of genes encoding GLUT and hexokinase proteins. In NELPC, elevated expression of GCK (encoding glucokinase protein) and decreased expression of SLC2A12 correlated with earlier biochemical recurrence. In tumors treated with AR-inhibitors, high expression of GCK and low expression of SLC2A12 correlated with NE histopathology and PSMA gene suppression. GLUT12-suppression and amplification of glucokinase was observed in NE-induced PC cell lines and PDX models. A higher glucose uptake was confirmed in low-PSMA tumors using a GB2-Cy3 probe in a zebrafish model. Conclusion: NE gene signature in NEPC and NELPC associates with a distinct transcriptional profile of GLUTs and HKs. PSMA-suppression correlates with GLUT12-suppression and glucokinase-amplification. Alteration of FDG uptake-associated genes correlated positively with higher glucose uptake in AR and PSMA-suppressed tumors. Zebrafish xenograft tumor models are an accurate and efficient pre-clinical method for monitoring non-radioactive glucose uptake.




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Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection using repeat PSMA-PET

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.




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18F-Fluorodeoxyglucose Positron Emission Tomography / Computed Tomography in Left-Ventricular Assist Device Infection: Initial Results Supporting the Usefulness of Image-Guided Therapy

Background: Accurate definition of the extent and severity of left-ventricular assist device (LVAD) infection may facilitate therapeutic decision making and targeted surgical intervention. Here, we explore the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for guidance of patient management. Methods: Fifty-seven LVAD-carrying patients received 85 whole-body 18F-FDG PET/CT scans for the work-up of device infection. Clinical follow-up was obtained over a period of up to two years. Results: PET/CT showed various patterns of infectious involvement of the 4 LVAD components: driveline entry point (77% of cases), subcutaneous driveline path (87%), pump pocket (49%) and outflow tract (58%). Driveline smears revealed staphylococcus or pseudomonas strains as the underlying pathogen in a majority of cases (48 and 34%, respectively). At receiver-operating characteristics analysis, an 18F-FDG standardized uptake value (SUV) >2.5 was most accurate to identify smear-positive driveline infection. Infection of 3 or all 4 LVAD components showed a trend towards lower survival vs infection of 2 or less components (P = 0.089), while involvement of thoracic lymph nodes was significantly associated with adverse outcome (P = 0.001 for nodal SUV above vs below median). Finally, patients that underwent early surgical revision within 3 months after PET/CT (n = 21) required significantly less inpatient hospital care during follow-up when compared to those receiving delayed surgical revision (n = 11; p<0.05). Conclusion: Whole-body 18F-FDG PET/CT identifies the extent of LVAD infection and predicts adverse outcome. Initial experience suggests that early image-guided surgical intervention may facilitate a less complicated subsequent course.




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Quantitative 3D assessment of 68Ga-DOTATOC PET/MRI with diffusion-weighted imaging to assess imaging markers for gastroendopancreatic neuroendocrine tumors: Preliminary results

68Ga-DOTATOC-PET/MRI (68Gallium-DOTATOC-positron emission tomography/magnetic resonance imaging) combines the advantages of PET in the acquisition of metabolic-functional information with the high soft tissue contrast of MRI. Standardized uptake values (SUV) in tumors were suggested as a measure of somatostatin receptor expression. A challenge with receptor ligands is, that the distribution volume is confined to tissues with tracer-uptake, potentially limiting SUV quantification. In this study, different functional, three-dimensional (3D) SUV, apparent diffusion coefficient (ADC) parameters and arterial tumor enhancement were tested for the characterization of gastroendopancreatic neuroendocrine tumors (GEP-NET). Methods: For this single-center, cross-sectional study, 22 patients with 24 histologically confirmed GEP-NET lesions (15 men/7 women; median, 61 years, range, 43-81 years), who received hybrid 68Ga-DOTA-PET/MRI examinations at 3T between January 2017 and July 2019 met eligibility criteria. SUVs, tumor-to-background ratios (TBR), the total functional tumor volume (TFTV), ADCmean and ADCmin were measured based on volumes of interest (VOI) and examined with receiver operating characteristic analysis to determine cut-off values for differentiation between low and intermediate grade GEP-NET. Spearman’s rank correlation coefficients were used to assess correlations between functional imaging parameters. Results: The ratio of PET-derived SUVmean and diffusion-weighted imaging (DWI)-derived ADCmin was introduced as a combined variable to predict tumor grade, outperforming single predictors. Based on a threshold ratio of 0.03 to be exceeded, tumors could be classified as grade 2 with a sensitivity of 86% and specificity of 100%. SUV and functional ADC values as well as arterial contrast enhancement parameters showed non-significant and mostly negligible correlations. Conclusion: As receptor density and tumor cellularity appear to be independent, potentially complementary phenomena, the combined PET/MRI ratio SUVmean/ADCmin may be used as a novel biomarker, allowing to differentiate between grade 1 and 2 GEP-NET.




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Hyper-progressive Disease in Patients With Non-Small Cell Lung Cancer Treated With Checkpoint Inhibitors: The Role of 18F-FDG PET/CT

Introduction: A new pattern of response, so-called hyper-progressive disease (HPD), is emerging during treatment with immune checkpoint inhibitors (ICI). Our aim was to investigate the prevalence of such phenomenon and to assess its association with clinical variables and metabolic parameters by 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods: Data from 50 patients (34 male, 16 female, median age 73) with non-small cell lung carcinoma (NSCLC) and treated with ICI were prospectively collected. All patients underwent contrast-enhanced CT, 18F-FDG PET/CT, and complete peripheral blood sample at baseline before ICI. HPD was defined according to clinical and radiologic criteria. Because of the rapid disease progression or worsening of clinic conditions, radiologic response assessment was available for 46 patients. OS were analyzed using the Kaplan–Meier method and the log-rank test. A Cox proportional hazards regression analysis was used to evaluate factors independently associated with OS. Median follow-up was 12.4 months (9.7-15.2 months). Results: We identified the following response categories: 10 cases as complete/partial response (CR/PR), 17 cases with stable disease (SD), 5 patients with progressive disease (PD), and 14 with HPD. Among metabolic parameters we observed a statistically significant association between HPD status and tumor burden, expressed by both MTV (756.1ml for HPD vs 475.6ml for non-HPD, P = 0.011) and TLG (287.3 for HPD vs 62.1 for non-HPD, P = 0.042). Among clinical variables, 12/14 patients (85.7%) within the HPD group compared with 8/32 patients (25%) in the non-HDP group had more than two metastatic sites (p<0.001). In addition, the derived neutrophil-to-lymphocyte ratio (dNLR) and platelet counts was significantly associated with HPD status (P = 0.038, P = 0.025, respectively). Survival analysis showed a median OS of 4 months for HPD group compared with 15 months within non-HPD patients (P = 0.003). Likewise, median OS was significantly different when we considered all the response categories: CR/PR, SD, PD, and HPD (P = 0.001). Finally, Multivariate analysis identified MTV and dNLR as independent predictors for OS. Conclusion: Our results suggest that the use of ICI might represent a concern in patients with high metabolic tumor burden and inflammatory indexes at baseline. However Additional studies are needed.




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SUVmax-V for assessing treatment response in FDG-PET Imaging of Patient-Derived Tumor Xenografts involving Triple-Negative Breast Cancer




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PET/CT imaging with a 18F-labeled galactodendritic unit in a galectin-1 overexpressing orthotopic bladder cancer model

Galectins are carbohydrate-binding proteins overexpressed in bladder cancer (BCa) cells. Dendritic galactose moieties have a high affinity for galectin-expressing tumor cells. We radiolabeled a dendritic galactose carbohydrate with fluorine-18 – 18F-labeled galactodendritic unit 4 – and examined its potential in imaging urothelial malignancies. Methods: The 18F-labeled 1st generation galactodendritic unit 4 was obtained from its tosylate precursor. We conducted in vivo studies in galectin-expressing UMUC3 orthotopic BCa model to determine the ability of 18F-labeled galactodendritic unit 4 to image BCa. Results: Intravesical administration of 18F-labeled galactodendritic unit 4 allowed specific accumulation of the carbohydrate radiotracer in galectin-1 overexpressing UMUC3 orthotopic tumors when imaged with PET. The 18F-labeled galactodendritic unit 4 was not found to accumulate in non-tumor murine bladders. Conclusion: The 18F-labeled galactodendritic unit 4 and similar analogs may be clinically relevant and exploitable for PET imaging of galectin-1 overexpressing bladder tumors.